CN104093768B - 导入有苯基硼酸基的嵌段共聚物及其使用 - Google Patents
导入有苯基硼酸基的嵌段共聚物及其使用 Download PDFInfo
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
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- 239000002540 palm oil Substances 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
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- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
- A61K47/6455—Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/40—Polyamides containing oxygen in the form of ether groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/42—Polyamides containing atoms other than carbon, hydrogen, oxygen, and nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/28—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polyamides (AREA)
Applications Claiming Priority (3)
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| US201161561022P | 2011-11-17 | 2011-11-17 | |
| US61/561,022 | 2011-11-17 | ||
| PCT/JP2012/079897 WO2013073697A1 (ja) | 2011-11-17 | 2012-11-19 | フェニルボロン酸基が導入されたブロックコポリマーおよびその使用 |
Publications (2)
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| CN104093768A CN104093768A (zh) | 2014-10-08 |
| CN104093768B true CN104093768B (zh) | 2016-09-21 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX348798B (es) | 2011-03-31 | 2017-06-29 | Nanocarrier Co Ltd | Composicion farmaceutica que contiene copolimero en bloque que comprende compuesto de acido boronico. |
| JP6195171B2 (ja) | 2012-04-27 | 2017-09-13 | 国立大学法人 東京大学 | 核酸デリバリー用ユニット構造型医薬組成物 |
| US10232054B2 (en) | 2014-02-12 | 2019-03-19 | Accurna, Inc. | Composition for mRNA delivery |
| US10993960B1 (en) | 2014-05-08 | 2021-05-04 | Kawasaki Institute Of Industrial Promotion | Pharmaceutical composition |
| KR101891655B1 (ko) * | 2016-05-17 | 2018-08-24 | 기초과학연구원 | 페닐보론산이 결합된 고분자를 포함하는 약물 전달체 |
| EP3495406A4 (en) * | 2016-08-02 | 2020-04-01 | Nippon Kayaku Kabushiki Kaisha | ACTIVE TARGETING TYPE POLYMER DERIVATIVE, COMPOSITION CONTAINING SAID POLYMER DERIVATIVE, AND USES OF SAID POLYMER DERIVATIVE AND COMPOSITION THEREOF |
| EP3501544B1 (en) * | 2016-08-22 | 2021-07-28 | Tokyo Institute of Technology | Ligand capable of multivalently binding to glutamine transporter, and composition comprising same |
| US11324835B2 (en) | 2017-08-31 | 2022-05-10 | Kawasaki Institute Of Industrial Promotion | Nucleic acid-loaded unit polyion complex |
| KR102075476B1 (ko) * | 2017-12-29 | 2020-02-10 | 포항공과대학교 산학협력단 | 페닐보론산이 결합된 고분자를 포함하는 하이드로겔 |
| EP3788094A2 (en) | 2018-04-27 | 2021-03-10 | Genedit Inc. | Cationic polymer and use for biomolecule delivery |
| EP3978078A4 (en) * | 2019-05-29 | 2023-08-02 | Tokyo Institute of Technology | Complex, medicine, therapeutic agent for cancer, kit and conjugate |
| AU2020348451A1 (en) | 2019-09-20 | 2022-04-21 | Glyscend, Inc. | Substituted phenyl boronic acid containing polymers and methods of use |
| WO2022191107A1 (ja) * | 2021-03-10 | 2022-09-15 | Ａｇｃ株式会社 | 含ハロゲン部位を有するポリマーおよび該ポリマーを用いた医薬組成物 |
| CN114163591B (zh) * | 2021-11-29 | 2023-08-01 | 南方医科大学 | 一种嵌段共聚物、嵌段共聚物载药胶束及其制备方法和应用 |
| CN114533669B (zh) | 2022-01-18 | 2022-11-04 | 武汉大学 | 一种口腔护理组合物及其制备方法和应用 |
| CN114632145B (zh) * | 2022-03-07 | 2024-02-27 | 浙江大学 | 一种负载胰岛素的苯硼酸/脂肪酸双改性ε-聚赖氨酸颗粒及其制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05301880A (ja) * | 1992-04-22 | 1993-11-16 | Nippon Oil & Fats Co Ltd | フェニルボロン酸誘導体及び製造方法 |
| JPH083172A (ja) * | 1994-06-15 | 1996-01-09 | Nippon Oil & Fats Co Ltd | フェニルボロン酸誘導体および製造方法 |
| JP2002179683A (ja) * | 2000-12-13 | 2002-06-26 | Japan Science & Technology Corp | ポリアミノ酸誘導体から成る核酸関連物質反応試薬 |
| WO2009133647A1 (ja) * | 2008-05-02 | 2009-11-05 | 国立大学法人筑波大学 | 高分子化環状二トロキシドラジカル化合物およびその使用 |
| JP2011173960A (ja) * | 2010-02-23 | 2011-09-08 | Univ Of Tsukuba | 高分子ミセル型光刺激応答性一酸化窒素供与体 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| JP4781435B2 (ja) | 2006-10-19 | 2011-09-28 | ナノキャリア株式会社 | 薬剤複合体用ブロック共重合体及び医薬組成物 |
| EP2131814A4 (en) | 2007-02-26 | 2011-08-03 | Wisconsin Alumni Res Found | POLYMIC MICROMS FOR THE RELEASE OF ACTIVE COMPOUNDS |
| KR20110026424A (ko) | 2008-05-13 | 2011-03-15 | 유니버시티 오브 워싱톤 | 중합체 캐리어 |
| JP4538666B2 (ja) | 2008-07-29 | 2010-09-08 | ナノキャリア株式会社 | 薬物内包アクティブターゲット型高分子ミセル、医薬組成物 |
| US8557292B2 (en) | 2008-08-13 | 2013-10-15 | California Institute Of Technology | Carrier nanoparticles and related compositions, methods and systems |
| WO2010114770A1 (en) | 2009-03-30 | 2010-10-07 | Cerulean Pharma Inc. | Polymer-agent conjugates, particles, compositions, and related methods of use |
| JP5622188B2 (ja) * | 2010-01-05 | 2014-11-12 | 独立行政法人物質・材料研究機構 | フェニルボロン酸系単量体及びフェニルボロン酸系重合体 |
| MX348798B (es) | 2011-03-31 | 2017-06-29 | Nanocarrier Co Ltd | Composicion farmaceutica que contiene copolimero en bloque que comprende compuesto de acido boronico. |
-
2012
- 2012-11-19 BR BR112014011831A patent/BR112014011831A2/pt not_active IP Right Cessation
- 2012-11-19 KR KR1020147013186A patent/KR101912978B1/ko not_active Expired - Fee Related
- 2012-11-19 RU RU2014124333/04A patent/RU2014124333A/ru not_active Application Discontinuation
- 2012-11-19 WO PCT/JP2012/079897 patent/WO2013073697A1/ja active Application Filing
- 2012-11-19 CA CA2853902A patent/CA2853902A1/en not_active Abandoned
- 2012-11-19 ES ES12850688.8T patent/ES2603632T3/es active Active
- 2012-11-19 IN IN3580CHN2014 patent/IN2014CN03580A/en unknown
- 2012-11-19 JP JP2013529476A patent/JP5481614B2/ja not_active Expired - Fee Related
- 2012-11-19 AU AU2012337721A patent/AU2012337721B2/en not_active Ceased
- 2012-11-19 EP EP12850688.8A patent/EP2781536B1/en not_active Not-in-force
- 2012-11-19 MX MX2014005540A patent/MX2014005540A/es unknown
- 2012-11-19 US US14/358,816 patent/US9114177B2/en not_active Expired - Fee Related
- 2012-11-19 CN CN201280056639.0A patent/CN104093768B/zh not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05301880A (ja) * | 1992-04-22 | 1993-11-16 | Nippon Oil & Fats Co Ltd | フェニルボロン酸誘導体及び製造方法 |
| JPH083172A (ja) * | 1994-06-15 | 1996-01-09 | Nippon Oil & Fats Co Ltd | フェニルボロン酸誘導体および製造方法 |
| JP2002179683A (ja) * | 2000-12-13 | 2002-06-26 | Japan Science & Technology Corp | ポリアミノ酸誘導体から成る核酸関連物質反応試薬 |
| WO2009133647A1 (ja) * | 2008-05-02 | 2009-11-05 | 国立大学法人筑波大学 | 高分子化環状二トロキシドラジカル化合物およびその使用 |
| JP2011173960A (ja) * | 2010-02-23 | 2011-09-08 | Univ Of Tsukuba | 高分子ミセル型光刺激応答性一酸化窒素供与体 |
Non-Patent Citations (1)
| Title |
|---|
| フエニルボロン酸を內核に結合させたPEG-p（Lys）ブロツク共重合体ミセルの調製とその外部環境応答性;中野渡史子，原田敦史，片岡一則;《高分子学会予稿集》;19991231;第48卷(第3期);572 * |
Also Published As
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| AU2012337721A1 (en) | 2014-05-22 |
| BR112014011831A2 (pt) | 2017-05-09 |
| US9114177B2 (en) | 2015-08-25 |
| AU2012337721B2 (en) | 2015-12-10 |
| ES2603632T3 (es) | 2017-02-28 |
| CA2853902A1 (en) | 2013-05-23 |
| IN2014CN03580A (enrdf_load_stackoverflow) | 2015-10-09 |
| EP2781536A4 (en) | 2015-06-10 |
| RU2014124333A (ru) | 2015-12-27 |
| CN104093768A (zh) | 2014-10-08 |
| US20150051347A1 (en) | 2015-02-19 |
| EP2781536A1 (en) | 2014-09-24 |
| MX2014005540A (es) | 2014-09-22 |
| EP2781536B1 (en) | 2016-08-17 |
| JPWO2013073697A1 (ja) | 2015-04-02 |
| KR101912978B1 (ko) | 2018-10-29 |
| KR20140106511A (ko) | 2014-09-03 |
| JP5481614B2 (ja) | 2014-04-23 |
| WO2013073697A1 (ja) | 2013-05-23 |
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